Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial

• Conditions: Adenocarcinoma; Colorectal Neoplasms; Gastrointestinal Neoplasms; Rectal Diseases; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Digestive System Diseases

• Registration Number: NCT01995942
• Lead Sponsor: Royal Marsden NHS Foundation Trust

Brief Summary

Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Current treatments may benefit from new genetic information relating to the cancer. We hope to identify genetic differences in certain types of rectal cancer which will allow future treatments.

Detailed Description

Neoadjuvant chemoradiotherapy (CRT) is widely accepted as beneficial to selected patients in terms of decreased risk of local recurrence and overall survival. Current management of rectal cancer involves risk stratification through pre-operative staging leading to formulation of treatment strategy. Very little is known about the long-term outcomes and response to CRT on MRI detected extramural venous invasion (mrEMVI). Although mrEMVI is accepted as a marker of poor prognosis, whether it has a predictive value and should be specifically treated is not known.

Molecular and genetic profiling provides us with an opportunity to understand the underlying mechanisms which govern clinical behaviour in rectal cancer. Using high-throughput technology such as tissue microarray analysis allows large-scale analysis of specimens in a relatively short amount of time. It offers the ability to compare the molecular profiles of different subtypes of rectal cancer such as mrEMVI-positive and -negative tumours and whether any changes are observed following CRT. This can then be correlated with clinical behaviour over the medium and long-term with regards to local recurrence, distant metastases and overall survival.

This study will identify important differences between key rectal cancer tumour subtypes. Identification of reliable pathological markers of EMVI pathways (from both the primary tumour sample, but more importantly from the pre-operative biopsies) has real potential for taking us a step closer to more personalised management of rectal cancer by establishing prognostic biomarkers reflective of disease type, but also through the underlying biology that may be highlighted (with its promise of therapeutic translation).

Study Timeline

• Study Start: 2013-06-07
• Study First Submitted: 2013-11-21
• Study First Submitted QC: 2013-11-26
• Study First Posted: 2013-11-27
• Primary Completion: 2017-02-02
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-13
• Last Update Posted: 2018-09-14
• Study Completion: 2022-02-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 246

Inclusion Criteria

1. Locally advanced primary rectal cancer (requiring pre-operative treatment); diagnosed on tissue biopsy
2. Adult patients - over 18 years
3. Able to undergo curative (TME) surgery
4. Able to undergo MRI and CT with relevant contrast agent
5. Able to undergo LCRT

Exclusion Criteria

1. Metastatic disease at presentation
2. Emergency diagnosis/treatment
3. Unable to undergo staging (MRI and CT) or treatment procedures (LCRT/surgery)

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years.	3 years

Secondary Outcome Measures

Name	Time	Method
Response rates (in terms of mrTstage, mrN stage, involvement of CRM (circumferential resection margin) and mrTRG (tumour regression grade)) in addition to recurrence rates at 1 year and 3 years.	3 years
Measurement of the change in mrEMVI from pre to post pre-operative therapy, will be based on a new proposed EMVI-TRG classification (EMVI TRG 1-5).	5 months	mrEMVI Regression Grade Scoring Table: Grade 5 - No response (intermediate signal intensity, same appearances as original tumour) Grade 4 - Slight response (little areas of fibrosis or mucin but mostly tumour) Grade 3 - Moderate response (\>50% fibrosis or mucin, and visible intermediate signal) Grade 2 - Good response (dense fibrosis; no obvious residual tumour, signifying minimal residual disease or no tumour) Grade 1 - Radiological complete response (rCR) (linear/crescentic 1-2mm scar in mucosa or submucosa only.)

Trial Locations

Locations (19)

Derriford Hospital; 🇬🇧 Plymouth, Devon, United Kingdom

Royal Surrey County Hospital; 🇬🇧 Guildford, Surrey, United Kingdom

Croydon University Hospital; 🇬🇧 Thornton Heath, Surrey, United Kingdom

Salisbury District Hospital; 🇬🇧 Salisbury, Wiltshire, United Kingdom

George Eliot Hospital; 🇬🇧 Nuneaton, United Kingdom

Alexandra Hospital; 🇬🇧 Redditch, United Kingdom

South Warwickshire NHS Foundation Trust (Warwick Hospital); 🇬🇧 Warwick, United Kingdom

Peterborough City Hospital; 🇬🇧 Peterborough, Cambridgeshire, United Kingdom

Royal Cornwall Hospital; 🇬🇧 Truro, Cornwall, United Kingdom

Queen's Hospital, Burton Upon Trent; 🇬🇧 Burton-on-Trent, Staffordshire, United Kingdom

Homerton University Hospital; 🇬🇧 London, Surrey, United Kingdom

University Hospital Coventry; 🇬🇧 Coventry, West Midlands, United Kingdom

Leighton Hospital; 🇬🇧 Crewe, Cheshire, United Kingdom

Poole Hospital; 🇬🇧 Poole, Dorset, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, Hampshire, United Kingdom

North Manchester General Hospital; 🇬🇧 Crumpsall, Manchester, United Kingdom

Kings Mill Hospital; 🇬🇧 Sutton-in-Ashfield, Nottinghamshire, United Kingdom

University Hospital of South Manchester; 🇬🇧 Wythenshawe, Manchester, United Kingdom

Royal Marsden Hospital; 🇬🇧 London And Surrey, United Kingdom